Possibly the first case of onychomycosis by Fusarium lactis: Case presentation and literature review of onychomycosis by Fusarium species.

Fusarium species (spp.) is frequently found in soil and plant residues and on plant bodies in all climatic zones worldwide. Although there have been few reports of onychomycosis caused by Fusarium spp., it is characterized by drug sensitivity and other characteristics. Here, we report what may be the first case of onychomycosis caused by Fusarium lactis. We analyzed the mycology and characterized previously reported cases of onychomycosis caused by Fusarium spp. A 73-year-old otherwise healthy woman presented with discoloration and thickening of her right thumbnail with paronychia. Direct microscopy revealed unevenly swollen hyphae, and a Grocott-stained nail specimen showed septate hyphae. Based on the morphological features and gene analysis of fungus isolated from the nail, we diagnosed onychomycosis caused by F. lactis belonging to Fusarium fujikuroi species complex. Partial nail removal and topical application of 1% luliconazole solution resolved the condition in 6 months. Minimum inhibitory concentrations for isolated F. lactis showed high sensitivity to luliconazole but not itraconazole or terbinafine. The isolated F. lactis was temperature-sensitive. A search of the literature revealed 57 cases of onychomycosis caused by Fusarium spp. with delineated clinical characteristics. Since those cases were investigated using morphological and/or molecular methods, we analyzed them by species complex as well as species. Onychomycosis caused by Fusarium spp. is predominantly found on the big toe, with Fusarium solani species complex and Fusarium oxysporum species complex accounting for over 70% of cases. Infection of only one digit with paronychia is a characteristic clinical manifestation of onychomycosis caused by Fusarium spp. Since there has been an increase in instances of molecular determination of Fusarium spp., it is deemed necessary to clarify its clinical and fungal nature. Due to its characteristic drug sensitivity and temperature-sensitive nature, new treatments are expected to be developed.

[Trichophyton tonsurans Infection].

Trichophyton tonsurans infection has been prevalent among individuals involved in contact sports in Japan since about 2000. The present review focuses on its diagnosis, molecular epidemiology, drug susceptibility, and infection control. The most commonly observed lesions of T. tonsurans, an anthropogenic dermatophyte, are tinea corporis and tinea capitis. However, the presence of asymptomatic carriers must be considered for infection control. Genotypic epidemiology using restriction fragment length polymorphisms (RFLP) in the non-transcribed spacer (NTS) region of the ribosomal RNA gene showed a lack of diversity of genotypes, and only the NTS I genotype is detected at present. In regard to drug susceptibility, terbinafine drug resistance has not been found to be associated with the RFLP genotypes, and it is assumed that there are no terbinafine-resistant strains in Japan. T. tonsurans coexisted with other fungi and bacteria in the scalp of asymptomatic carriers without affecting species diversity. T. tonsurans is an anthropogenic dermatophyte and may be difficult for the human immune system to eliminate. During an infection outbreak, screening of infection and treatment including asymptomatic carriers are essential to eradicate the infection.

Multilocus Microsatellite Analysis of the Molecular Epidemiology of Microsporum canis Isolated in Japan.

Microsporum canis, a major causative agent of zoonotic dermatophytosis, has become prevalent in Japan. Molecular epidemiological surveys using multilocus microsatellite typing (MLMT), a sensitive genotyping tool for fungi, have been conducted to reveal intraspecies polymorphisms of M. canis.The present study utilized MLMT optimized for Japanese strains of M. canis to analyze epidemic trends of fungal infection. Six individual loci were targeted; namely, MS1, 2, 4, 5, 6, and 7. Analysis of data from 1974 through 2022 identified 416 strains, which were sorted into 60 genotypes by MLMT.The major genotypes showed changes in dominance during this period-changes that may reflect historical increases and decreases in the numbers of patients infected with M. canis patients. The main origins of infection included animal breeders and pet stores, as well as stray cat communities. Forty-nine episodes of familial outbreaks and cohabitant animal infections were recorded, and genotypes responsible for each episode were determined. MLMT analysis is not only a robust tool to understand population structures, but likely the most suitable method for tracking M. canis infections.

MALDI-TOF MS identification of Exophiala species isolated in Japan: Library enrichment and faster sample preparation.

Exophiala species cause chromoblastomycosis, mycetoma, and phaeohyphomycosis, which are occasionally fatally in immunocompromised patients. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) provides rapid and accurate examination of isolated bacteria and some fungal isolates, but the preparation method for filamentous fungi is complicated. In this study, 31 clinical isolates of Exophiala spp. in Japan were identified by MALDI-TOF MS with a library enriched by adding data. To simplify the sample preparation method, two modified methods were compared with the standard method for filamentous fungi. The agar cultivation sample preparation method reduced the time required for liquid culture and was considered suitable for clinical use. In 30 of 31 clinical isolates of Exophiala spp., the species identified by MALDI-TOF MS with the highest score matched the species identified by sequencing the internal transcribed spacer region. Exophiala dermatitidis, E. lecanii-corni, and E. oligosperma were identified above the genus level, while E. jeanselmei and E. xenobiotica were often not identified at the species level. The identification scores tended to be lower for less-registered strains in the in-house library. It is suggested that library enrichment and the modified preparation method may facilitate early diagnosis of rare fungal infections by Exophiala spp. in clinical laboratories using MALDI-TOF MS.

A Case of Oral Candidiasis Caused by Candida dubliniensis During Treatment of Humanized Monoclonal Antibody to Interleukin-17A.

We report the case of a 77-year-old woman who had been diagnosed with psoriasis vulgaris at another hospital at age 33 and treated with various therapies since then. At 61 years old, she was diagnosed with psoriatic arthritis with phalangitis, swelling of both hands, and sacroiliac arthritis, and was treated with oral immunotherapy. At age 76, treatment with a humanized monoclonal antibody to interleukin-17A (ixekizumab) was started due to increased pain associated with her hand inflammation. After ten months of this treatment, she visited our hospital with the complaint of tongue pain and white fungi on the tongue surface. Direct KOH examination of the fungi showed pseudomycelia and spores, and fungal culture (CHROMagar®Candida) showed green and dark green wet colonies. Sequencing of the D1D2 region of ribosomal RNA gene of the nuclear DNA of fungi from the colony identified Candida dubliniensis. She was treated with amphotericin B gargle (Fungizone®syrup) for two weeks, and the lesion improved. Since then, the patient has been treated with ixekizumab with no recurrence of oral candidiasis.

First Isolation of Neoscytalidium dimidiatum from Human Dermatomycosis in Japan.

Neoscytalidium dimidiatum is a common fungus that causes non-dermatophyte dermatomycosis in tropical regions, but there have been no reports of infection with N. dimidiatum in Japan. Here, we report the first isolation of N. dimidiatum from human dermatomycosis in Japan. A 62-year-old healthy Japanese male had been treated with oral terbinafine for tinea pedis diagnosed from a microscopic examination in 2003 with a lesion that was intractable. In 2020, re-identification by sequencing the internal transcribed spacer regions and the D1/D2 domain of the large-subunit (LSU) ribosomal RNA gene revealed that the pathogen was N. dimidiatum. Antifungal susceptibility tests showed that the minimum inhibitory concentration of the drug luliconazole (LLCZ) against the pathogen was 0.00049 µg/mL. The patient's lesions were cured by topical LLCZ. The clinical course and drug susceptibility suggest that LLCZ is a suitable first-line drug for treatment.

Polypoid Basal Cell Carcinoma on the Nose Tip.

Basal cell carcinoma (BCC) is usually seen on the face as a pigmented nodule. We herein report a patient who presented with a polypoid BCC on the nose tip. Clinically, we suspected adnexal tumor; however, the findings of dermoscopy were consistent with that of BCC. Although the tumor was excised at the stalk, it was completely resected. Since the clinical manifestation was characteristic, we reviewed previously reported polypoid BCCs and found that this tumor can occur at any site, including the trunk and inguinal region, which are not preferential sites for ordinary BCC. There have been no reports of polypoid BCC on the nasal tip. The initial diagnoses varied, including adnexal tumors, and dermoscopic examinations proved useful for suspecting polypoid BCC. Histopathologically, the tumor cells in the resected specimens were within the polypoid area. Although BCC is a common tumor, polypoid BCC has distinct clinical features, and we should keep this rare subtype in mind.

Change in dominant genotype of Microsporum canis, a causative fungus of zoonotic dermatophytosis, in Japan over the past 40 years.

Multilocus microsatellite typing was performed on 124 strains of Microsporum canis, which is the most prevalent causative fungus of zoonotic dermatophytosis, isolated in Japan between 1974 and 1981. The strains had been enclosed in glass ampoules by freeze dried process. Genotypes were detected by capillary electrophoresis targeted on six microsatellite regions, and 19 genotypes were found among these 124 strains. The most frequent genotype, which had been reported as genotype L in a previous study, comprised 56 of the 124 strains (45.2%), although genotype L was reported to comprise only six of 165 strains (3.6%) isolated between 2010 and 2017. A decrease in the prevalence of genotype L may have led to the retreat of M. canis infection in 1996 to 2006. On the other hand, genotype A, the second most predominant genotype in the aforementioned studies of strains isolated between 2010 and 2017, comprised just four of 124 strains (3.2%) in the present study. Thus, these studies reveal that prevalences of some major genotypes have changed over the last 40 years. Genotype consistency of strains was proven in all of 12 familial cases, each of which was infected with a single genotype. We emphasize the importance of fungal culture collection for further studies with new techniques in the future.

Genotyping of Trichophyton tonsurans strains isolated between 2016 and 2020, and terbinafine susceptibility of the species in Japan.

Trichophyton tonsurans is the most prevalent fungus which causes dermatophytosis among contact sports players in Japan. We previously surveyed the epidemic of T. tonsurans in Japan from early 2000, and determined the genotypes of isolates by analysis of restriction enzyme fragment length polymorphisms in the non-transcription spacer (NTS) region of ribosomal RNA gene, which enabled discrimination of eight genotypes, namely NTS I to NTS VIII. In the present study, we performed genotyping of T. tonsurans isolated between 2016 and 2020, and investigated the trend of the epidemic and resistance of the pathogen to antibiotic terbinafine (TBF). Regardless of which contact sport they played, the genotype of all 123 strains of T. tonsurans isolated from athletes was NTS I. Genotypes NTS II and III, which were isolated in considerable numbers mainly from wrestlers between 2000 and 2015, were conspicuously absent. TBF susceptibility was screened in 237 T. tonsurans strains isolated between 2000 and 2020 with 28 of these further assessed for minimum inhibitory concentration of TBF and squalene epoxidase gene sequences. None of the strains showed TBF resistance. TBF may still be effective to control the epidemic of T. tonsurans.

Scalp microbiota in members of a Japanese high school judo team including Trichophyton tonsurans carriers.

Trichophyton tonsurans is a major causative fungus of human dermatophytosis, which has been isolated from contact sport players in Japan. The microbiome in the scalp of judoists with or without T. tonsurans infection was analyzed to investigate the correlation between T. tonsurans infection and microbiome profile. Among 30 members of the same judo team in a high school, samples were collected by scrubbing their scalp with shampoo hairbrushes; then, DNA was extracted directly from the obtained scales. Twenty-seven datasets were subjects for microbiome analysis and T. tonsurans was detected in six members (no T. tonsurans-positive participants had scalp lesions). Regarding the fungal microbiome, Cyphellophora were more abundant in the T. tonsurans-positive group (TP) than T. tonsurans-negative group (TN) (P < 0.05). Regarding the Malassezia microbiome, Malassezia caprae were more abundant in TP than TN (P < 0.01). Regarding the bacterial microbiome, Lactococcus, Actinobacillus, Beijerinckiaceae and Xanthomonas were more abundant in TP than TN (P < 0.05). Also, the Shannon diversity index revealed no significant diversity between TP and TN, and 3-D principal coordinate analysis revealed no clear separation between TP and TN. There was practically no difference in microbiome between TP and TN, indicating that T. tonsurans could colonize humans regardless of their original microbiome. T. tonsurans coexisted with other fungi and bacteria without affecting species diversity in asymptomatic carriers. To our knowledge, this is the first investigation of the correlation between T. tonsurans infection and microbiome profile.

Disseminated cutaneous cryptococcosis in an immunocompetent elderly long-term pigeon fancier.

Cutaneous cryptococcosis is classified as localized cutaneous cryptococcosis and cutaneous manifestations of disseminated cryptococcosis. The former presents as lesions, confined to isolated parts of the skin, which are neither systemically disseminated nor associated with cryptococcal fungemia or antigenemia. The latter presents as lesions through dissemination of Cryptococcus from visceral organs such as the lungs, with most cases being immunosuppressed hosts. We report the case of an immunocompetent elderly long-term pigeon fancier who presented with disseminated cutaneous cryptococcosis caused by Cryptococcus neoformans. Although the patient had been at risk of inhaling the pathogen by keeping pigeons for many years, and had been treated with topical steroids for a localized nodular lesion, the cause of development of multiple skin lesions could not be determined. The patient paradoxically showed no pulmonary or central nervous system symptoms, fungemia or glucuronoxylomannan antigenemia. Treatment with oral itraconazole 200 mg/day was not effective, but combination therapy of 5-fluorocytosine 200 mg/kg per day and fluconazole 100 mg/day resolved the disease.